A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX202 in Patients with Advanced Solid Tumors
This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety, tolerability, and efficacy of XTX202, an engineered IL-2 prodrug with its activity masked, as monotherapy in patients with advanced solid tumors. Phase 1 Part 1a will examine XTX202 monotherapy in an accelerated and standard 3+3 dose-escalation design. Based on the results of Part 1a, Part 1b will be initiated to further examine XTX202 in patients with select advanced solid tumors and to further characterize XTX202. Based on results of Phase 1 patients with select advanced solid tumors will be enrolled in Phase 2.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
95
XTX202 Monotherapy
UC San Diego Moores Cancer Center
La Jolla, California, United States
Norris Comprehensive Cancer Center
Los Angeles, California, United States
Incidence of Dose Limiting Toxicities (DLTs) (Phase 1 Part 1A Only)
All participants in Phase 1 Part 1A (Dose Escalation) who received at least 1 dose of XTX202 and experienced a DLT. DLTs were defined as the following: * Any treatment-related Grade ≥ 3 toxicity * Any Grade febrile neutropenia * The following nonhematologic exceptions: * Grade 3 nausea or vomiting lasting \< 3 days * Grade 3 fatigue lasting \< 7 days * Any treatment-related toxicity that resulted in a treatment delay of ≥ 7 days
Time frame: Cycle 1 day 1 up to just prior to the second dose of study drug at Cycle 2 day 1 (each cycle is 21 days)
Incidence of Treatment-emergent Adverse Events (Phase 1 Only)
Treatment-emergent adverse event (TEAE) is defined as any adverse event that starts or increases in severity on or after the first dose of study drug and no later than 90 days after the last dose of study drug. Adverse events are graded using the NCI CTCAE version 5.0.
Time frame: Up to 24 months
Investigator-assessed Objective Response Rate (ORR) Per RECIST 1.1 (Phase 2 Only)
Percentage of participants who achieved at least one confirmed Complete Response (CR) or Partial Response (PR). Response is based on Investigator assessment according to RECIST v1.1. In the analysis set used for ORR, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: Up to 24 months
Incidence of Changes in Clinical Laboratory Values (Phase 1 Only) - Biochemistry
Number of participants that experienced a clinical laboratory test abnormality. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Baseline is defined as the last available measurement taken prior to the first administration of study treatment. Laboratory data is graded using the NCI CTCAE version 5.0. Participants are included only once, in the highest level of CTCAE Grade.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of California Los Angeles
Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian- Newport Beach
Newport Beach, California, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Moffitt Cancer Center
Tampa, Florida, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
HealthPartners Cancer Center at Regions Hospital
Saint Paul, Minnesota, United States
Atlantic Health System/Morristown Medical Center
Morristown, New Jersey, United States
...and 5 more locations
Time frame: Up to 24 months
Incidence of Changes in Clinical Laboratory Values (Phase 1 Only) - Hematology
Number of participants that experienced a clinical laboratory test abnormality. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Baseline is defined as the last available measurement taken prior to the first administration of study treatment. Laboratory data is graded using the NCI CTCAE version 5.0. Participants are included only once, in the highest level of CTCAE Grade.
Time frame: up to 24 months
Incidence of Changes in Clinical Laboratory Values (Phase 1 Only) - Thyroid Function
Number of participants with shift from baseline in laboratory results. Baseline is defined as the last available measurement taken prior to the first administration of study treatment. Participants with both baseline and at least one postbaseline result are included. Participants are included only once, in the highest level of CTCAE Grade. Missing = number of patients with missing baseline and/or post baseline laboratory value.
Time frame: Up to 24 months
Incidence of Changes in Clinical Laboratory Values (Phase 1 Only) - Coagulation
Number of participants with shift from baseline in laboratory results. Baseline is defined as the last available measurement taken prior to the first administration of study treatment. Participants with both baseline and at least one postbaseline result are included. Participants are included only once, in the highest level of CTCAE Grade. Missing = number of patients with missing baseline and/or post baseline laboratory value. Missing = number of patients with missing baseline and/or post baseline laboratory value
Time frame: Up to 24 months
Investigator-assessed Objective Response Rate (ORR) Per RECIST 1.1 (Phase 1 Only)
Percentage of participants who achieved at least one confirmed Complete Response (CR) or Partial Response (PR). Response will be based on Investigator's assessment according to RECIST v1.1.
Time frame: Up to 24 months
Duration of Response (DOR) (Phase 2 Only)
Duration of response is defined as time from first documentation of a subsequently confirmed objective response (CR or PR) to the date of the first documentation of radiographic disease progression according to Investigator assessment by RECIST v1.1, or death due to any cause, whichever occurs first. Participants who do not have an observed documented disease progression or death from any cause will be censored at the latest tumor response assessment date.
Time frame: Up to 24 months
Disease Control Rate (Phase 2 Only)
Disease Control Rate (DCR) is defined as percentage of participants with confirmed BOR of CR, PR or SD (minimum duration of 6 weeks) according to RECIST v1.1, after the first dose of study treatment. In the analysis set used for DCR, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: Up to 24 months
Overall Survival (OS) (Phase 2 Only)
OS is defined as the time from first administration of study treatment to death due to any cause. For participants without a record of death, OS will be censored at the date they were last known alive. In the analysis set used for OS, participants are assigned to a treatment group based on the initial dose received.. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group
Time frame: Up to 24 months
Progression-free Survival (PFS) (Phase 2 Only)
PFS is defined as the time from first administration of study treatment until first documentation of radiographic PD according to RECIST v1.1, or death due to any cause, whichever occurs first. Participants who do not have an observed documented disease progression or death from any cause will be censored at the latest tumor response assessment date. In the analysis set used for PFS, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group
Time frame: Up to 24 months
Incidence of Treatment-emergent Adverse Events (Phase 2 Only)
Treatment-emergent adverse event is defined as any adverse event (AE) that starts or increases in severity on or after the first dose of study drug and no later than 90 days after the last dose of study drug. AEs are graded using the NCI CTCAE version 5.0.
Time frame: Up to 24 months
Incidence of Changes in Clinical Laboratory Values (Phase 2 Only) - Hematology
Number of participants that experienced a clinical laboratory test abnormality. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Baseline is defined as the last available measurement taken prior to the first administration of study treatment. Laboratory data is graded using the NCI CTCAE version 5.0. Participants are included only once, in the highest level of CTCAE Grade.
Time frame: Up to 24 months
Incidence of Changes in Clinical Laboratory Values (Phase 2 Only) - Biochemistry
Number of participants that experienced a clinical laboratory test abnormality. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Baseline is defined as the last available measurement taken prior to the first administration of study treatment. Laboratory data is graded using the NCI CTCAE version 5.0. Participants are included only once, in the highest level of CTCAE Grade.
Time frame: Up to 24 months
Incidence of Changes in Clinical Laboratory Values (Phase 2 Only) - Thyroid Function
Number of participants with shift from baseline in laboratory results. Baseline is defined as the last available measurement taken prior to the first administration of study treatment. Participants with both baseline and at least one postbaseline result are included. Participants are included only once, in the highest level of CTCAE Grade. Missing = number of patients with missing baseline and/or post baseline laboratory value.
Time frame: Up to 24 months
Incidence of Changes in Clinical Laboratory Values (Phase 2 Only) - Coagulation
Number of participants with shift from baseline in laboratory results. Baseline is defined as the last available measurement taken prior to the first administration of study treatment. Participants with both baseline and at least one postbaseline result are included. Participants are included only once, in the highest level of CTCAE Grade. Missing = number of patients with missing baseline and/or post baseline laboratory value.
Time frame: Up to 24 months
Plasma Concentrations of Total XTX202
Plasma Concentration of Total XTX202 by Nominal Time (h) From End of Infusion Following a Single IV Administration of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: 0.00, 0.0167, 0.250, 0.500, 1.50, 3.00, 24.0, 72.0, 144, 312, 504 hours post-dose following a single administration of XTX202 on Cycle 1
Plasma Concentrations of Intact XTX202
Plasma Concentration of Intact XTX202 by Nominal Time (h) From End of Infusion Following a Single IV Administration of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: 0.00, 0.0167, 0.250, 0.500, 1.50, 3.00, 24.0, 72.0, 144, 312, 504 hours post-dose following a single administration of XTX202 on Cycle 1
Total XTX202 Plasma Trough Concentration
Plasma Trough Concentration of Total XTX202 Following Multiple IV Administrations of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group
Time frame: From Cycle 1 to up to Cycle 18 (21 days per cycle)
Intact XTX202 Plasma Trough Concentration
Plasma Trough Concentration of Intact XTX202 Following Multiple IV Administrations of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: from Cycle 1 to up to Cycle 18 (21 days per cycle)
Maximum Observed Plasma Concentration (Cmax) of Total XTX202
Cmax following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Maximum Observed Plasma Concentration (Cmax) of Intact XTX202
Cmax following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Time of Maximum Observed Concentration (Tmax) of Total XTX202
Time of maximum observed concentration (Tmax) of total XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Time of Maximum Observed Concentration (Tmax) of Intact XTX202
Time of maximum observed concentration (Tmax) of intact XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Area Under the Curve From Time 0 to 504 Hours (AUC0-504) of Total XTX202
Area under the curve (AUC)of total XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Area Under the Curve From Time 0 to 504 Hours (AUC0-504) of Intact XTX202
Area under the curve (AUC) of intact XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Half-life (T1/2) of Total XTX202
Half-life (T1/2) of total XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Half-life (T1/2) of Intact XTX202
Half-life (T1/2) of intact XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Systemic Clearance (CL) of Total XTX202
Systemic clearance (CL) of Total XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Systemic Clearance (CL) of Intact XTX202
Systemic clearance (CL) of intact XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Volume of Distribution (Vd) of Total XTX202
Volume of distribution (Vd) of total XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Volume of Distribution (Vd) of Intact XTX202
Volume of distribution (Vd) of intact XTX202 following a single IV infusion of XTX202. In the analysis set used for PK, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: up to 21 days following a single IV infusion of XTX202 on Cycle 1
Antidrug Antibody (ADA) Occurrence and Titer in Serum (Phase 1 Only)
Overall ADA Incidence Following a Single IV Administration of XTX202 In the analysis set used for ADA, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 1 Part 1B initially received XTX202 2.8 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: from Cycle 1 Day 1 to up to 24 months
Incidence and Persistence of ADAs (Including Neutralizing ADAs) and Titers (Phase 2 Only)
Overall ADA Incidence Following a Single IV Administration of XTX202. In the analysis set used for ADA, participants are assigned to a treatment group based on the initial dose received. In the Participant Flow module, participants are assigned to a treatment group based on the highest dose received. One participant in Phase 2 Part 2B initially received XTX202 1.4 mg/kg, then increased the dose to 4.0 mg/kg at a later cycle and was therefore included in the XTX202 4.0 mg/kg dose group.
Time frame: From Cycle 1 Day 1 to up to 24 months